Perioperative Tislelizumab Combined With Nab-Paclitaxel for Muscle-invasive Urothelial Bladder Carcinoma

NCT04730219 | Unknown Phase 2

• 1 other identifier: TRUCE-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study to determine the safety and efficacy of tislelizumab when given in combination with nab-paclitaxel as perioperative treatment in patients with muscle-invasive bladder cancer (MIBC) prior to cystectomy or complete TURBT. Patients will receive treatment with tislelizumab in combination with nab-paclitaxel every 3 weeks for 3 treatment cycles over 9 weeks followed by standard radical cystectomy or complete TURBT.

Conditions

Muscle Invasive Bladder Cancer; Urothelial Carcinoma

Keywords

neoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response (cCR) rate

  defined as the absence of tumor residual confirmed by surgery (RC-PLND or complete TURBT), negative urine cytology and no evidence of lymph nodes or distant metastasis on imaging.

  At the time of complete transurethral resection of bladder tumor or radical cystectomy (within 12 weeks of the first dose of tislelizumab)

Secondary Outcomes (5)

• Objective response rate (ORR)

  At the time of complete transurethral resection of bladder tumor or radical cystectomy (within 12 weeks of the first dose of tislelizumab)

• Event-free survival (EFS)

  up to 3 years

• Overall Survival (OS)

  up to 3 years

• Disease-specific survival (DSS)

  up to 3 years

• Number of adverse events and severity by grade (CTCAE)

  up to 1 years

Study Arms (1)

Tislelizumab and Nab Paclitaxel

EXPERIMENTAL

Tislelizumab 200mg IV on day 1 in combination with nab paclitaxel 200mg IV on day 2 every 3 weeks for 3 cycles followed by surgery.

Drug: Tislelizumab; Drug: Nab paclitaxel

Interventions

Tislelizumab DRUG

Tislelizumab 200mg will be administered on Day 1 every 3 weeks for 3 cycles

Also known as: BGB-A317

Tislelizumab and Nab Paclitaxel

Nab paclitaxel DRUG

Nab paclitaxel 200mg will be administered on Day 2 every 3 weeks for 3 cycles

Tislelizumab and Nab Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Ability to comply with the protocol.
• Age ≥ 18 years.
• Suitable and planned for complete transurethral resection of bladder tumor or radical cystectomy
• Histopathologically confirmed urothelial carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) urothelial cell pattern.
• Clinical stage T2-T4a N0 M0 disease by CT (or MRI). If the clinical stage is T2-4aN1-3M0, it must be judged by the investigator. If it is judged that radical surgery can still be performed, it can be included in the study.
• Expected survival time is greater than 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 1 or 2.
• Agree to provide tissue examination specimens (used to detect PD-L1 expression, tumor mutation burden, etc.)
• The organ function level must meet the following requirements:
• Hematological indicators: absolute neutrophil count ≥1.5×10\^9/L, platelet count ≥80×10\^9/L, hemoglobin ≥6.0 g/dL (can be maintained by symptomatic treatment);
• Liver function: total bilirubin ≤ 1.5 times the upper limit of normal value, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal value, if there is intrahepatic transaminase ≤ 5 times the upper limit of normal value;
• Renal function: creatinine ≤ 2 times the upper limit of normal, and creatinine clearance ≥ 30 ml/min;

You may not qualify if:

• Receive live attenuated vaccines within 4 weeks before treatment or plan to receive live attenuated vaccines during the study period.
• Active, known or suspected autoimmune diseases.
• Known history of primary immunodeficiency.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Female patients who are pregnant or breastfeeding.
• Untreated acute or chronic active hepatitis B or C infection. In the case of patients receiving antiviral therapy, the doctor will judge whether they are eligible for enrollment according to the individual conditions of the patient while monitoring the virus copy number.
• Have used immunosuppressive drugs in the past 4 weeks before starting treatment, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroids (that is, prednisolone or equivalent physiological doses of no more than 10 mg/day) Other corticosteroids).
• Those who are known or suspected to be allergic to tislelizumab and nab paclitaxel.
• Have a clear history of active tuberculosis.
• Have received PD-1/PD-L1/CTLA-4 antibody or other immunotherapy in the past.
• Those who are participating in other clinical research.
• Reproductive men or women who are likely to become pregnant have not taken reliable contraceptive measures.
• Uncontrolled concurrent diseases include but are not limited to:
• HIV-infected persons (HIV antibody positive).
• Serious infections that are active or poorly clinically controlled.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (1)

Tianjin Medical University Second Hospital

Tianjin, Tianjin Municipality, 300211, China

Location

Related Publications (2)

• Shen C, Chai W, Han J, Zhang Z, Liu X, Yang S, Wang Y, Wang D, Wan F, Fan Z, Hu H. Identification and validation of a dysregulated TME-related gene signature for predicting prognosis, and immunological properties in bladder cancer. Front Immunol. 2023 Oct 27;14:1213947. doi: 10.3389/fimmu.2023.1213947. eCollection 2023.

  PMID: 37965307 DERIVED

• Shen C, Bi Y, Chai W, Zhang Z, Yang S, Liu Y, Wu Z, Peng F, Fan Z, Hu H. Construction and validation of a metabolism-associated gene signature for predicting the prognosis, immune landscape, and drug sensitivity in bladder cancer. BMC Med Genomics. 2023 Oct 26;16(1):264. doi: 10.1186/s12920-023-01678-6.

  PMID: 37880682 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

tislelizumab; Taxes

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Officials

• Hailong Hu, MD,PhD

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 29, 2021
• Study Start: July 11, 2020
• Primary Completion: February 1, 2024
• Study Completion: July 1, 2024
• Last Updated: November 30, 2022

Record last verified: 2022-11

Locations

CN (1)